Reducing risk behaviours after stroke: An overview of reviews interrogating primary study data using the Theoretical Domains Framework

Background Lifestyle changes, in addition to preventive medications, optimise stroke secondary prevention. Evidence from systematic reviews support behaviour-change interventions post-stroke to address lifestyle-related risk. However, understanding of the theory-driven mediators that affect behaviour-change post-stroke is lacking. Methods Electronic databases MEDLINE, Embase, Epistemonikos and Cochrane Library of Systematic Reviews were searched to March 2023 for systematic reviews addressing behaviour-change after stroke. Primary studies from identified systematic reviews were interrogated for evidence supporting theoretically-grounded interventions. Data were synthesized in new meta-analyses examining behaviour-change domains of the Theoretical Domains Framework (TDF) and secondary prevention outcomes. Results From 71 identified SRs, 246 primary studies were screened. Only 19 trials (N = 2530 participants) were identified that employed theoretically-grounded interventions and measured associated mediators for behaviour-change. Identified mediators mapped to 5 of 14 possible TDF domains. Trial follow-up ranged between 1–12 months and no studies addressed primary outcomes of recurrent stroke or cardiovascular mortality and/or morbidity. Lifestyle interventions targeting mediators mapped to the TDF Knowledge domain may improve the likelihood of medication adherence (OR 6.08 [2.79, 13.26], I2 = 0%); physical activity participation (OR 2.97 [1.73, 5.12], I2 = 0%) and smoking cessation (OR 10.37 [3.22, 33.39], I2 = 20%) post-stroke, supported by low certainty evidence; Lifestyle interventions targeting mediators mapping to both TDF domains of Knowledge and Beliefs about Consequences may improve medication adherence post-stroke (SMD 0.36 [0.07, 0.64], I2 = 13%, very low certainty evidence); Lifestyle interventions targeting mediators mapped to Beliefs about Capabilities and Emotions domains may modulate low mood post-stroke (SMD -0.70 [-1.28, -0.12], I2 = 81%, low certainty evidence). Conclusion Limited theory-based research and use of behaviour-change mediators exists within stroke secondary prevention trials. Knowledge, Beliefs about Consequences, and Emotions are the domains which positively influence risk-reducing behaviours post-stroke. Behaviour-change interventions should include these evidence-based constructs known to be effective. Future trials should address cardiovascular outcomes and ensure adequate follow-up time.


Introduction
Stroke, the leading cause of adult acquired disability, has a 20% risk of recurrence within five years [1].A quarter of these recurrent events occur in the first year post-stroke, with an average annual risk thereafter of 4% [2].Poorer prognosis and greater disability are associated with recurrent events, highlighting the need for effective risk reduction measures [1,3].Population attributable, modifiable risk factors account for up to 90% of stroke risk [4].These include: hypertension, physical activity, dyslipidaemia, diet, central adiposity, psychosocial factors (home and/or work stress, life events and depression), current smoking, cardiac causes, high/ heavy episodic alcohol consumption and diabetes mellitus.Modifiable risk factors for (recurrent)stroke are amenable to lifestyle change [5].A modelling study suggests that lifestyle changes in diet and physical activity levels alongside optimized pharmacotherapy, could reduce five-year recurrent event rates after stroke by 80% [6].Initiating and sustaining lifestyle changes to mitigate the risk of recurrent events constitute complex behaviours entailing multiple interacting components at individual, social and environmental levels [3,7,8].Aspects such as knowledge, intentions, self-efficacy, motivation, outcome expectancies, perceived susceptibility/severity and social influences can act as barriers or facilitators to effective change [9].These are classified as determinants of behaviour and can act as mediators for change, defined as 'the intermediary variables in the causal process between an intervention and the behaviour change effect' [10].
Whilst published SRs broadly address the efficacy of lifestyle-based interventions poststroke [11][12][13][14][15], uncertainty remains about what works and why.Inclusion of studies lacking theory and understanding of determinants of health-related behaviours in stroke, may have influenced their findings.Failing to critically examine the role of these determinants as the mediators to affect behaviour, limits our understanding of effective interventions in stroke secondary prevention.An aligned overview of reviews [16], providing a best-evidence synthesis of behaviour-change interventions after stroke, highlighted the further need to delineate theorybased interventions and provide greater insight into why some interventions identified were effective or ineffective.This requires a better understanding of the role of theory and associated mediators in affecting behaviour-change [17,18].International secondary prevention guidelines recommend using theory-based lifestyle interventions [19], mirrored in the Medical Research Council (MRC) guidance on complex interventions where program theory is deemed essential to maximize the efficiency, use and impact of behaviour-change research [20].
Explicit use of theory in the design and evaluation of interventions in stroke secondary prevention presents this opportunity to understand why interventions work, for whom, and in what context [18].Selecting one or more theories as the basis for intervention development can prove challenging, partly due to often overlapping theoretical constructs [21].The Theoretical Domains Framework (TDF) is a comprehensive theory-informed approach to understanding the determinants of behaviour change and the factors influencing intervention development.The TDF was developed to allow theories and their constructs to be synthesised into groupings to make behaviour-change theories more accessible in intervention design and analysis [21,22].This is important as it provides a systematic and rigorous framework for understanding behaviour change in multiple populations and settings.Comprising 87 component parts across fourteen overarching domains of Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, Optimism, Beliefs about Consequences, Reinforcement, Intentions, Goals, Memory, Attention and Decision Processes, Environmental Context and Resources, Social Influences, Emotions, and Behavioural Regulation [22], the TDF provides comprehensive coverage of the possible mediators influencing behaviour-change.Tabular representation of the TDF describes these domains as they pertain to stroke secondary prevention in the current study (S1 Table ).
This overview of reviews aims to unpack complex interventions identified in primary studies across published SRs addressing behaviour-change post-stroke, to enable a better understanding of the underlying factors necessary to achieve the desired outcomes.Included primary studies are interrogated to identify the role of theory and proposed mediators for change, as mapped to the TDF domains.New meta-analyses synthesize primary studies by behaviourchange theoretical domains and secondary prevention outcomes, allowing the certainty of existing evidence supporting the working components of interventions to be examined.To our knowledge, the TDF has not previously been used as the basis from which to understand the behaviour-change constructs of effective stroke secondary prevention interventions.

Specific objectives
• Provide a compendium of theoretically-grounded primary studies identified across published SRs addressing secondary stroke prevention, using behavioural/self-management interventions.
• Extract the active components of reported interventions under the Template for Intervention description and Replication (TIDieR) [23] checklist, notably the theoretical perspectives described and the mediator/s for behaviour-change identified and measured.
• Synthesize the results from the identified primary studies by behaviour-change theoretical domains and secondary prevention outcomes.
• Determine the quality of evidence supporting the behaviour-change interventions and their working components by assigning a Grading of Recommendations Assessment, Development and Evaluation (GRADE) [24] of evidence for meta-analyses conducted.

Methods
This overview of reviews adheres to the preferred reporting guideline for overviews of reviews of healthcare interventions (PRIOR) statement and checklist (S2 Table) [25].It was preceded by an a priori published protocol [26] which detailed a two-phased approach.Phase one, published elsewhere [16], identifies, synthesises and provides GRADE [24] of certainty for published meta-analytic evidence.Phase 2, reported here, first identifies primary study level data from all published SRs employing theoretically-grounded behaviour-change and/or self-management interventions and then synthesises these data in new meta-analyses to examine evidence supporting the mediators for behaviour-change in affecting positive changes in secondary prevention outcomes.A theoretically-grounded study was considered, for the purposes of this review, to be one that identified a theoretical perspective and identified and measured mediator/s for the targeted behaviour-change [27] that mapped to the TDF domains.

Inclusion/Exclusion criteria
SRs of randomized control trials (RCTs) or cluster RCTs (CRCT) testing interventions for behaviour-change and/or self-management of risk in stroke secondary prevention were first identified.Primary studies included in these reviews were then considered where the following were detailed: • Adult population comprising stroke/TIA Exclusion criteria applied: • Interventions designed to alter care process or health professionals' education/practice.
• Interventions not targeting behaviour-change in stroke secondary prevention.

• Telehealth interventions
• Interventions targeting family/partner dyads, unless behaviour-change in the person with stroke was specifically targeted and extractable.

Search strategy
Using a comprehensive search strategy compiled in conjunction with a liaison librarian, electronic databases MEDLINE, Embase, Epistemonikos and Cochrane Library of Systematic Reviews were systematically searched from inception to March 2023 with no limitations applied.For databases not specific to systematic reviews (Medline, Embase), a third methodological search string for systematic reviews was included.These two databases were chosen as they are two of the largest health focussed databases and we were confident, based on our experience and previous searches that they would contain the reviews we were looking for.In addition, reference lists of included SRs were checked.It is possible that more recent RCTs, not yet reviewed in SRs are not included.The full search strategy which targeted published systematic reviews is provided (S1 File).

Screening and selection
Identified SRs were screened at title and abstract stages by two independent reviewers.An inclusive approach was taken whereby if it was unclear whether the SR met the inclusion criteria, it progressed to the next stage.Full manuscripts were next reviewed independently for inclusion by two reviewers.SRs were included where they reported RCTs of behaviourchange/self-management interventions and reported secondary prevention outcomes of mortality, recurrent stroke, other cardiovascular events; health/lifestyle behaviours; emotional selfregulation; as summarized in the stroke secondary prevention model underpinning the overview (S1 Fig).
While phase 1 of this overview [16] excluded SRs that did not meet explicit criteria (i.e.no meta-analyses or where meta-analyses included mixed populations), phase 2 included any SR that contained primary RCTs of interest.All primary studies were subsequently screened for eligibility by two reviewers (PH, OL) to ensure they met the specific RCT study-level inclusion criteria listed above and that none of the following exclusion criteria applied: • Interventions designed to alter care process or health professionals' education/practice.
• Interventions not targeting behaviour-change in stroke secondary prevention.

• Telehealth interventions
• Interventions targeting family/partner dyads, unless behaviour-change in the person with stroke was specifically targeted and extractable.
Following screening of RCTs from identified SRs, each trial intervention, as described in the paper, was examined for inclusion against domains 1 and 2 of the TIDieR checklist [23].These relate specifically to providing the rationale for the intervention and the theoretical perspective.Where theory and rationale were provided, the next level screening identified whether a mediator for behaviour-change, mapping to the TDF, was identified and measured.Studies that did not measure proposed mediator/s pre and post intervention were excluded.Any disagreements regarding study eligibility were resolved by discussion to reach consensus.

Data extraction
Data from included RCTs were independently extracted and cross-checked by two reviewers (PH, OL).These data included TIDieR checklist domains (1-10); mediators for behaviourchange; TDF domain of the mediator; participants' characteristics (e.g.age, gender, time poststroke); reported stroke secondary prevention outcomes.

Quality appraisal
The Cochrane Risk of Bias (ROB) [28] tool was used to assess the methodological quality of included RCTs.Where trials were appraised using this tool in the SR of origin, it was accepted and extracted by reviewers.Where more than one SR presented ROB for the same trial and a discrepancy between reviews was identified, the more conservative ROB was recorded.Where trials were appraised in the SR of origin using an alternative tool or where no appraisal was documented, two reviewers (PH, OL) independently appraised the trial using the Cochrane ROB tool to ensure conformity.

Data synthesis
Meta-analyses, conducted using Review Manager 5 (RevMan5) [29], grouped data by TDF domains and secondary prevention outcomes, where data presented permitted.For continuous data, where different scales assessed the same outcome, standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated.SMD is used as a summary statistic to measure effect size that quantifies differences in standard deviations between two groups.The Hedges' g version of SMD conducted here in RevMan5 is the preferred statistic when sample sizes are unequal and/or are small (< 20), as the case in the current study, as it takes each sample size into consideration when calculating the overall effect size.The inverse variance method was used as it is especially suitable when using SMD to minimise uncertainty of the overall effect size [30].
For dichotomous variables, odds ratios (OR) with 95% CIs were employed using the Mantel-Haenszel method.Random effects models were applied to provide a more conservative estimate of overall effect size as statistical heterogeneity was assumed [30].The I 2 statistic measured heterogeneity; >50% was considered substantial [30].To over-come a unit-of-analysis error, where multiple comparisons from the same study were included more than once in a meta-analysis, the group was split into separate groups with smaller sample sizes to avoid overcounting [31].Where included trials reported outcomes measured at more than one time point post-intervention, the last follow-up time was included in the meta-analysis.Where possible, sensitivity analysis was conducted, to examine pooled secondary prevention outcome data only from trials where the mediator for behaviour-change was observed to positively change.The certainty of the evidence for each effective intervention/outcome group identified was evaluated using the GRADE criteria [24] and agreed by consensus of two reviewers (PH and OL).

Description of included primary RCTs
Table 1 summarises the characteristics of all nineteen included RCTs.The trials were conducted across four geographical locations-Australia [33,38,40], North America [34,36,48], Asia [44,45,51,52] and Europe [35, 37, 39, 41-43, 46, 47, 50].When broken down by country and world bank classification all but two studies from an upper-middle-income economy (China) [51,52] originated in high-income nations [54].A total of 2530 participants with confirmed first or recurrent stroke/TIA were included across the trials.Seventeen trials included men and women, one included men only [41], and one did not report the gender of participants [35].Usual care was the comparator in most trials; however, four trials compared the intervention to alternate/active controls (e.g.computerised cognitive training [41]; education program [47]; stress management program without mindfulness [51]; non-medication related conversation [43].One trial was a three-arm trial [38] but only data from cognitive-behavioural therapy versus usual care is included here based on outcomes reported.Intervention follow-up ranged from immediate post-intervention to twelve months across the included RCTs. The interventions, as described in each study, differed considerably in terms of their rationale, active components, delivery, and theoretical underpinning, as documented under all TIDieR domains (S3 Table ).Secondary prevention outcomes that mapped to the prevention model (S1 Fig) [26] were extracted.Twelve stroke secondary prevention outcomes drawn from seven trials documented statistically significant effects.Significant heterogeneity of measures and scales employed across trials was evident, limiting meta-analyses that could be conducted.
Across the nineteen RCTs included, eight different mediators for behaviour-change were referenced and measured pre and post intervention.These mediators mapped to five of fourteen possible domains of the TDF, depicted in Fig 2 .Eight trials [34, 42-46, 51, 52] demonstrated a positive change in the mediator for change between the intervention group and control, of which five reported statistically significant effects in outcomes related to stroke secondary prevention [34,43,45,46,52].Others demonstrated improvement in both trial arms [36,41].

Quality appraisal
Risk of bias summary and graphical illustration of ROB assessments presented as percentages are included in supplemental material (S2 and S3 Figs).Principal sources of bias related to blinding of participants and personnel delivering interventions.As it is generally accepted that blinding of participants or interventionists would not be feasible in complex interventions, this criterion was not judged in the overall rating.Low ROB was judged where the criterion was met in remaining domains [46,48]; an unclear or moderate risk was judged where there was low or unclear ROB for these domains [36,37,41,43]; a high ROB was judged where there was high ROB in one or more domain [33-35, 38-40, 42, 44, 45, 47, 50-52].

Meta-analysis: Primary outcomes
Mortality, recurrent stroke, cardiovascular events.Despite describing their interventions as designed to reduce risk, no included trial reported outcomes of cardiovascular death, recurrent stroke or cardiovascular events, and follow-up was short ranging between 1-12 months.Mortality data, available from five trials [34,36,37,45,50], was reported under adverse events.Pooled data on 1203 participants (S4 Fig), as grouped by TDF domain, demonstrated no significant difference in the odds of death as an adverse event in lifestyle-related behaviour-change interventions when compared to controls (OR 0.60, 95% CI 0.32-1.11,p = 0.62, I 2 0%).

Health behaviour outcomes
Medication adherence.Five trials reported medication adherence as a risk reducing behavioural outcome [34,[43][44][45][46]. Data were pooled from two trials measuring frequency of selfreported adherence [34,46].Both trials used behaviour-change mediators mapped to the TDF Knowledge domain.Meta-analysis demonstrated a significant effect in favour of the intervention group (OR 6.08 [2.79, 13.26], p< 0.00001, I 2 0%) (Fig 3a).GRADE criteria identified low certainty of evidence (Table 2).As both trials demonstrated a positive change in the measured mediator, no further sensitivity analysis was conducted.
Two trials reported outcomes addressing salt or salty food consumption [45,46] and used behaviour-change mediators mapped to the TDF Knowledge domain.The units or mode of measurement employed did not allow data to be pooled.One of these trials [45] demonstrated a significant reduction in salted food consumption in the intervention group (p = 0.004).
Data were pooled from two trials [45,46] measuring self-reported achievement of physical activity targets and using behaviour-change mediators mapped to the TDF Knowledge domain.A significant effect in favour of the intervention was observed (OR 2.97 [1.73, 5.12], p< 0.0001, I 2 0%)(Fig 4c).GRADE criteria identified Low certainty evidence (Table 2).No Smoking cessation.Three trials addressed tobacco use post-stroke, employing behaviourchange mediators mapped to TDF domains of Knowledge [34,46] and Intention [48].Data were pooled for outcomes of smoking cessation rates post-intervention [34,46].Meta-analysis demonstrated a significantly higher likelihood of smoking cessation favouring the intervention group (OR 10.37 [3.22, 33.39], p < 0.0001, I 2 20%) (Fig 4d).Low GRADE certainty evidence was identified (Table 2).Both trials demonstrated positive changes in the mediator measured, negating further sensitivity analysis.
Alcohol consumption.Three trials reported safe alcohol consumption outcomes using behaviour-change mediators mapped to TDF domains of Knowledge [34,46] and Intentions [35].The units or mode of measurement employed in reported outcomes (alcohol abstinence, units consumed per week, percentage of self-reported alcohol reduction) did not allow data to be pooled.However, two trials demonstrating positive change in the mediator of Knowledge, reported significant alcohol abstinence rates (OR = 1.48, 1.36-1.53,p = 0.31) [34] and alcohol consumption reduction (OR = 4.48 [1.16, 17.29], p = 0.03) [46] in favour of the intervention group.The remaining trial [35], where the mediator mapped to the Intentions domain, demonstrated no effect.

Discussion
Use of theory and theoretical constructs is recommended to enhance effectiveness of complex interventions [17,55] and to allow greater understanding of behaviour-change processes [22].This overview of reviews, providing new meta-analyses, summarises the quantity and quality of evidence supporting theoretically-grounded interventions for behavioural change and/or self-management of health behaviours in stroke secondary prevention.As multiple behaviourchange theories exist, the TDF proved a useful theoretical lens through which theory-associated mediators for behaviour-change post-stroke could be viewed.Formal mediation analysis (indirect and direct paths) was beyond the scope of this current work, rather the effect of proposed mediators associated with behaviour-change interventions was examined.In excluding RCTs unless a theoretical perspective and an identified and measured mediator for behaviourchange was provided, trials with inadequately described theoretical underpinnings were omitted.This addresses current uncertainty in published meta-analysis, where ineffectiveness or conflicting results may result from underuse of theory and/or a lack of understanding of determinants of health behaviours post-stroke.
Across the nineteen RCTs identified in this review, three TDF domains were associated with impactful health behaviour-change: Knowledge (increased stroke knowledge); Beliefs about Consequences (greater understanding of benefits/rationale for preventive actions); and Emotions (self-regulation of emotional responses).Indeterminate effects were found, with considerable heterogeneity, for two other TDF domains, of Beliefs about Capabilities (self-confidence, self-efficacy in ability to put knowledge to constructive use) and Intentions (conscious decision to perform a behaviour).The identification of only five TDF domains from a possible fourteen points to significant underutilisation and measurement of theory-associated mediators in current trials.As no trials addressing outcomes of cardiovascular morbidity, recurrent stroke, or other cardiovascular events in stroke secondary prevention met the inclusion criteria, evidence is still lacking for these primary outcomes.An important observation about the role of mediators in achieving health behaviour-changes post-stroke is evident across the meta-analyses reported.With the exception of the outcome of depression, all other secondary prevention outcomes demonstrating a positive effect (medication adherence, achievement of physical activity targets, smoking cessation), were drawn from trials where the mediator for change was positively influenced by the intervention.Similarly for negative meta-analyses related to fruit and vegetable consumption, anxiety and psychological distress outcomes, the proposed mediators for change did not improve in the included trials.
It is important to note commonalities and discrepancies that exist between the results of previously published SRs [11][12][13][14][15], a best evidence synthesis from these reviews [16] and the results presented here.High-level evidence of published meta-analyses addressing behavioural change and/or self-management interventions in stroke secondary prevention found only moderate overlap of primary studies between reviews, and identified the SRs as addressing different intervention types, broadly categorized as Multimodal; Behavioural change; Self-management and Psychological therapies [16].This approach failed to delineate any theoretical overlap between the intervention types, or the specific mediators targeted in the interventions that were effective.The ability to replicate the intervention clinically and include the important theoretical domains by which to affect change remained challenging.This review now indicates that TDF domains of Knowledge, Beliefs about Consequences, and Emotions are important considerations for inclusion in secondary prevention interventions designed to achieve behaviour-change.
Current best-evidence identified in the TDF Knowledge domain is drawn from trials where mediators for behaviour-change included enhanced knowledge about the nature of stroke, risk factors, and consequences.Interventions provided interactive and tailored information on risk reducing behaviours; offered self-management information and support in goal setting to improve lifestyle habits; and provided information on self-monitoring in relation to maintaining behaviour-change.Four trials specified and measured stroke knowledge as the mediator for change associated with their intervention [33,34,45,46].Health behaviours that were successfully targeted through the mediator of stroke knowledge were medication adherence, physical activity participation, healthy eating, smoking and alcohol consumption.Published psychological determinants of medication adherence as a health behaviour, highlight the importance of knowledge for stroke survivors [56], noting greater knowledge is associated with better adherence to prescribed medication.Qualitative research further highlights that inadequate information about stroke and commonly prescribed preventive medications, pose significant patient-level barriers [57] and that passive written information provision was not a helpful means to improve adherence [58].A recent scoping review identified a mismatch between guideline recommendations for behavioural counselling and that audited in clinical practice, where the latter largely comprised information provision only [59].Making and sustaining behaviour-change is difficult to achieve.Information provision alone has been shown to be ineffective in affecting the mediator of knowledge and thus positive behaviour-change [60].Active rather than passive information provision, mirrored in the interventions of the included studies in this review, has been found to be effective [61].This current overview now provides definitive evidence to guide clinical practice in stroke secondary prevention in the use of active mechanisms of information provision, anchored in the Knowledge domain of the TDF.
Addressing individuals' Beliefs about Consequences of stroke-related behaviours was identified in this overview as an important TDF domain that can influence adherence to preventive medications and target self-regulation of mood.This now constitutes an important domain to address in stroke secondary prevention interventions where adherence rates with prescribed medications is poor [62] and low mood is associated with higher stroke recurrence rates [63] and mortality [1].Two trials identified in this overview sought to enhance individuals' beliefs and understanding of the benefits/rationale for preventive actions as their mediator for change [43,50] but for specific outcomes (e.g.medication adherence), evidence for this TDF domain relies on single study data [43].However, other research does support the relationship between perceived necessity for medications and adherence rates [56,57].
In the TDF Emotions domain, three distinct modifiable mediators (coping competence, sense of coherence and trait mindfulness) were identified in the five included trials targeting emotional self-regulation to reduce post-stroke risk [37,41,47,51,52].Of these, trait mindfulness, measured using MAAS, demonstrated positive change as the mediator to affect emotional self-regulation behaviour-change in two trials [51,52].Mindfulness, a state of awareness and attention to the present, has been shown by systematic review in stroke to derive benefits across psychological, physiological, and psychosocial outcomes including stroke secondary prevention targets of anxiety, depression and blood pressure [64].Therapeutic benefits of mindfulness for individuals post-stroke, both psychological and physical, are supported by a recent scoping review.However, caveats about knowledge gaps relating to Mindfulness-based Cognitive Therapy (MBCT) and the lack of methodological robust studies were highlighted [65].
The Beliefs about Capabilities TDF domain, with self-efficacy as the mediator for behaviour-change, was identified in five trials [38-40, 42, 44] and the Intentions TDF domain, using stages of change as the mediator, was identified in three trials [35,36,48].Whilst self-efficacy was the mediator most frequently employed in primary studies interrogated, no trial employing self-efficacy as the mediator, was associated with health behaviour-changes post-stroke.This finding was unexpected.Self-efficacy is a well-established predictor of behaviour-change relating to physical activity participation for example [10], with a recent prospective cohort study identifying self-efficacy as the strongest contributing factor to stroke/TIA survivors' intentions to change health behaviours [66].Perceived self-efficacy is the main causal determinant cited in Social Cognitive Theory [67], is the proposed mediator for change in The Stanford University Chronic Disease Self-Management programme [68] and the Bridges Stroke Self-Management Programme [69].Whilst individuals' self-efficacy may have responded positively to the interventions included in the current review, results did not translate to riskreducing behaviour-change.Likewise, included trials [35,48] with a mediator anchored in the TDF Intentions domain reported conflicting results between mediators and outcomes.This finding may relate, in part, to poor alignment between theory as a set of concepts and propositions that explain behaviour, and the subsequent use of this theory to then identify and target the determinants of behaviour to affect behaviour-change [27].This was not clearly articulated in the majority of included trials which also failed to measure all mediators cited in their theory or to link the intervention techniques employed to these constructs, as best practice recommends.
Risk of stroke, stroke recurrence and both short and long-term outcomes disproportionally affect low and middle-income countries [2] where healthcare systems are primarily focused on acute care [70] and inconsistencies in ongoing care and service delivery exist [71].In addition, deprived or disadvantaged populations within high-income countries where modifiable risk factors are prevalent, experience disparities [72].Factors such as income, education, social support or isolation, ethnicity, and environmental conditions have been identified as confounding variables that need to be addressed in intervention studies [73,74].One study included in the current review showed a positive change in tobacco and alcohol use with African American and Hispanic participants of low socioeconomic status [34].However, despite the disproportionate burden of stroke on low and middle-income countries, the majority of the papers reviewed originated in high-income countries, limiting the generalisability of the findings.Whilst beyond the scope of this overview, we recognise the need for a better understanding and management of the gap observed between high-and low-income nations when designing and delivering effective stroke secondary prevention interventions.
Overall, results from this overview, which interrogated primary study-level data, need to be interpreted carefully.Despite a rigorous mediator identification process and mapping to an established framework (TDF), an element of subjectivity in this process remains.This is largely dependent on interpreting the definitions and descriptions provided in the primary studies and the mediator measured.Because strict criteria were applied for trial inclusion, evidence identified was often downgraded to low or very low due to the limited number of studies, small sample sizes, and risks of bias.Nevertheless, having GRADE for all included effective interventions is a strength of this overview.The limited number of trials available results, in the main, from unclear reporting of behaviour-change interventions in the RCTs screened, a recurrent issue in the extant literature.The growing number of complex and multicomponent interventions focusing on stroke secondary prevention [75], when recently scrutinised using the updated MRC Framework [20], identified only a small proportion providing a theoretical underpinning, and none reporting their proposed mediators of action or specifying behaviour-change techniques [75].Studies included in this overview presented wide variations in intervention content and delivery, timing after stroke, duration, location, and outcomes targeted, reflecting many of the challenges inherent in developing and reporting complex interventions in stroke secondary prevention [76].The small number of trials identified, despite the large volume of SRs, highlights a lack of standardisation in how behaviour-change and self-management interventions are reported, particularly in relation to describing their rationale and theoretical perspectives (points 1 and 2 of the TIDieR checklist [23]).
Future studies should endeavour to describe their behaviour-change interventions in a structured way.This should lay out the use of theory, the theory-related mediator/s targeted to affect behaviour-change, alongside the matched behaviour-change techniques employed.To this end, using TDF domains to select evidence-based behaviour-change techniques (BCT) as the active ingredients of an intervention [77] has evolved with an extensive taxonomy of BCTs available to draw from [78], and recent advances in behaviour-change intervention ontologies to aid the development of effective interventions [79].Future trials in behaviour-change for stroke secondary prevention, in addition to attending to how the intervention is developed and described, need to include outcomes that measure longer-term cardiovascular outcomes as well as behaviour-change, as these features were markedly absent in the reviewed literature.

Conclusion
This overview highlights the current lack of theory-based research and limited use of behaviour-change mediators within stroke secondary prevention trials.The findings identify the theoretical domains of Knowledge, Beliefs about Consequences, and Emotions as having utility in affecting positive changes in risk reducing health behaviours post-stroke to actively increase knowledge and awareness of all aspects of stroke and risk-reducing behaviours; address health beliefs and correct any misperceptions; and support emotional self-regulation.Taken together with the findings from a best-evidence synthesis previously published [16], the active components of successful strategies in theoretically-based behaviour-change and self-management interventions are better explained.Future research should, at a minimum, include these constructs known to be effective, in well conceptualised RCTs, with adequate follow-up time, that include primary outcomes addressing cardiovascular risk in addition to health behaviours.

Fig 4 .
Fig 4. Forest Plot: Lifestyle interventions versus usual care for the outcome of achieving physical activity participation targets (panel c); Lifestyle interventions versus usual care and/or active control for the outcome of smoking cessation (panel d).https://doi.org/10.1371/journal.pone.0302364.g004

Beliefs about capabilities and Emotions domains(assessed with: HADS, HAMD, MAAS)
. studies were rated as unclear in multiple risk of bias domains and high risk of bias related to blinding CI: confidence interval; OR: odds ratio; SMD: standardised mean difference MMAS: Moriskey Medication Adherence Scale; MARS: Medication Adherence Rating Scale; HADS: Hospital Anxiety and Depression Scale; HAMD: Hamilton depression rating scale; MAAS: Mindful Attention Awareness Scale Explanations: a. high risk of bias in multiple domains assessed in Cochrane risk of bias tool b. small number of included studies c